Chronobiologie des Blutdrucks und Chronopharmakotherapie der arteriellen Hypertonie

 

 Buy Article Permissions and Reprints

Zusammenfassung

Der Blutdruck ist einem zirkadianen Rhythmus unterworfen, der zu einer nächtlichen Absenkung führt. Bei Diabetes, Niereninsuffizienz, linksventrikulärer Hypertrophie, Schlafapnoe, Schwangerschaftshypertonie und verschiedenen sekundären Hypertonieformen kann die nächtliche Absenkung aufgehoben oder in ihr Gegenteil verkehrt sein. Die Diagnostik erfolgt mit Hilfe der 24-h-Blutdruckmessung, die aber in der Praxis noch zu selten für eine klinische Einschätzung des Patienten und die Therapiesteuerung herangezogen wird. Eine Anpassung der Auswahl und des Einnahmezeitpunkts der antihypertensiven Pharmakotherapie im Hinblick auf den zirkadianen Rhythmus wirkt sich günstig auf die Blutdruckkontrolle und die kardiovaskuläre Morbidität aus. Das gilt vor allem für Patienten mit fehlendem nächtlichem Blutdruckabfall oder einem Anstieg, bei denen die abendliche Medikation zu einer Normalisierung des Blutdrucks und der Wiederherstellung der physiologischen zirkadianen Rhythmik beitragen kann. Die vorliegende Arbeit gibt einen aktuellen Überblick zur Chronopharmakotherapie der arteriellen Hypertonie und gibt praktische Empfehlungen zur Umsetzung dieser Erkenntnisse im klinischen Alltag.

Abstract

Arterial blood pressure is subject to a circadian rhythm that results in a fall of blood pressure during the night. In patients with diabetes, renal insufficiency, left-ventricular hypertrophy, sleep apnea, hypertension of pregnancy, and different forms of secondary hypertension a nocturnal fall of blood pressure is even abandoned or reverted. Diagnosis is made using 24-h blood pressure measurement, which is however used not frequently enough for a clinical assessment or adjustment of therapy. An adaption of the selection or the time of administration of antihypertensive drugs with respect to the circadian rhythm is beneficial to control blood pressure and reduce cardiovascular morbidity. This is particularly true for patients with an a non- or inverted dipping blood pressure pattern, in which the bedtime dosing may result in a normalization of blood pressure and restoration of a normal circadian rhythm. The present manuscript reviews the chronopharmacotherapy of arterial hypertension and grant practical recommendations for their translation into clinical practice.

• Literatur

• 1 Brotman DJ, Davidson MB, Boumitri M et al. Impaired diurnal blood pressure variation and all-cause mortality. Am J Hypertens 2008; 21: 92-97
  CrossrefPubMedGoogle Scholar
• 2 de Leeuw PW, Falke HE, Kho TL et al. Effects of beta-adrenergic blockade on diurnal variability of blood pressure and plasma noradrenaline levels. Acta Med Scand 1977; 202: 389-392
  PubMedGoogle Scholar
• 3 Dolan E, Stanton A, Thijs L et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension 2005; 46: 156-161
  CrossrefPubMedGoogle Scholar
• 4 Fagard RH, Thijs L, Staessen JA et al. Night-day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension. J Hum Hypertens 2009; 23: 645-653
  CrossrefPubMedGoogle Scholar
• 5 Hermida RC, Ayala DE, Fernandez JR et al. Chronotherapy improves blood pressure control and reverts the nondipper pattern in patients with resistant hypertension. Hypertension 2008; 51: 69-76
  CrossrefPubMedGoogle Scholar
• 6 Hermida RC, Ayala DE, Fontao MJ et al. Chronotherapy with valsartan/amlodipine fixed combination: improved blood pressure control of essential hypertension with bedtime dosing. Chronobiol Int 2010; 27: 1287-1303
  CrossrefPubMedGoogle Scholar
• 7 Hermida RC, Ayala DE, Mojon A et al. Reduction of morning blood pressure surge after treatment with nifedipine GITS at bedtime, but not upon awakening, in essential hypertension. Blood Press Monit 2009; 14: 152-159
  CrossrefPubMedGoogle Scholar
• 8 Hermida RC, Ayala DE, Mojon A et al. Comparison of the effects on ambulatory blood pressure of awakening versus bedtime administration of torasemide in essential hypertension. Chronobiol Int 2008; 25: 950-970
  CrossrefPubMedGoogle Scholar
• 9 Hermida RC, Ayala DE, Mojon A et al. Chronotherapy with nifedipine GITS in hypertensive patients: improved efficacy and safety with bedtime dosing. Am J Hypertens 2008; 21: 948-954
  CrossrefPubMedGoogle Scholar
• 10 Hermida RC, Ayala DE, Mojon A et al. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int 2010; 27: 1629-1651
  CrossrefPubMedGoogle Scholar
• 11 Hermida RC, Ayala DE, Portaluppi F. Circadian variation of blood pressure: the basis for the chronotherapy of hypertension. Adv Drug Deliv Rev 2007; 59: 904-922
  CrossrefPubMedGoogle Scholar
• 12 Hermida RC, Calvo C, Ayala DE et al. Treatment of non-dipper hypertension with bedtime administration of valsartan. J Hypertens 2005; 23: 1913-1922
  CrossrefPubMedGoogle Scholar
• 13 Hurwitz S, Cohen RJ, Williams GH. Diurnal variation of aldosterone and plasma renin activity: timing relation to melatonin and cortisol and consistency after prolonged bed rest. J Appl Physiol 2004; 96: 1406-1414
  CrossrefPubMedGoogle Scholar
• 14 Kario K, Hoshide S, Shimizu M et al. Effect of dosing time of angiotensin II receptor blockade titrated by self-measured blood pressure recordings on cardiorenal protection in hypertensives: the Japan Morning Surge-Target Organ Protection (J-TOP) study. J Hypertens 2010; 28: 1574-1583
  CrossrefPubMedGoogle Scholar
• 15 Kario K, Matsuo T, Kobayashi H et al. Nocturnal fall of blood pressure and silent cerebrovascular damage in elderly hypertensive patients. Advanced silent cerebrovascular damage in extreme dippers. Hypertension 1996; 27: 130-135
  CrossrefPubMedGoogle Scholar
• 16 Koopman MG, Koomen GC, Krediet RT et al. Circadian rhythm of glomerular filtration rate in normal individuals. Clin Sci (Lond) 1989; 77: 105-111
  PubMedGoogle Scholar
• 17 Langner B, Lemmer B. Circadian changes in the pharmacokinetics and cardiovascular effects of oral propranolol in healthy subjects. Eur J Clin Pharmacol 1988; 33: 619-624
  CrossrefPubMedGoogle Scholar
• 18 Lemmer B. Chronopharmacology and controlled drug release. Expert Opin Drug Deliv 2005; 2: 667-681
  CrossrefPubMedGoogle Scholar
• 19 Lemmer B. Zirkadiane Rhythmen und klinische Pharmakologie. Internist (Berl) 2004; 45: 1006-1020
  PubMedGoogle Scholar
• 20 Lemmer B. The importance of circadian rhythms on drug response in hypertension and coronary heart disease – from mice and man. Pharmacol Ther 2006; 111: 629-651
  CrossrefPubMedGoogle Scholar
• 21 Li P, Sur SH, Mistlberger RE et al. Circadian blood pressure and heart rate rhythms in mice. Am J Physiol 1999; 276: R500-504
  PubMedGoogle Scholar
• 22 Luders S, Franz IW, Hilgers KF et al. Langzeitblutdruckmessung. Dtsch Med Wochenschr 2005; 130: 2664-2668
  Article in Thieme ConnectPubMedGoogle Scholar
• 23 Mancia G, De Backer G, Dominiczak A et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007; 25: 1105-1187
  CrossrefPubMedGoogle Scholar
• 24 Marques FZ, Campain AE, Davern PJ et al. Genes influencing circadian differences in blood pressure in hypertensive mice. PLoS One 2011; 6: e19203
  CrossrefPubMedGoogle Scholar
• 25 Middeke M. Antihypertensive Chronotherapie. Grundlage renaler Hochdruckformen ist häufig ein gestörter Tag-Nacht-Rhythmus. Dialyse aktuell 2010; 14: 98-103
  Article in Thieme ConnectPubMedGoogle Scholar
• 26 Middeke M. Arterielle Hypertonie. Stuttgart – New York: Georg Thieme Verlag; 2005
  Google Scholar
• 27 Middeke M. ABDM richtig interpretieren: Was wissen wir über Dipper und Non-Dipper?. MMW Fortschr Med 2006; 148: 51-52
  PubMedGoogle Scholar
• 28 Middeke M, Kluglich M, Holzgreve H. Chronopharmacology of captopril plus hydrochlorothiazide in hypertension: morning versus evening dosing. Chronobiol Int 1991; 8: 506-510
  CrossrefPubMedGoogle Scholar
• 29 Millar-Craig MW, Bishop CN, Raftery EB. Circadian variation of blood-pressure. Lancet 1978; 1: 795-797
  PubMedGoogle Scholar
• 30 Miller BH, McDearmon EL, Panda S et al. Circadian and CLOCK-controlled regulation of the mouse transcriptome and cell proliferation. Proc Natl Acad Sci U S A 2007; 104: 3342-3347
  CrossrefPubMedGoogle Scholar
• 31 Nold G, Strobel G, Lemmer B. Morning versus evening amlodipine treatment: effect on circadian blood pressure profile in essential hypertensive patients. Blood Press Monit 1998; 3: 17-25
  PubMedGoogle Scholar
• 32 Parving HH, Lehnert H, Brochner-Mortensen J et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345: 870-878
  CrossrefPubMedGoogle Scholar
• 33 Pierdomenico SD, Bucci A, Costantini F et al. Circadian blood pressure changes and myocardial ischemia in hypertensive patients with coronary artery disease. J Am Coll Cardiol 1998; 31: 1627-1634
  CrossrefPubMedGoogle Scholar
• 34 Portaluppi F, Smolensky MH. Perspectives on the chronotherapy of hypertension based on the results of the MAPEC study. Chronobiol Int 2010; 27: 1652-1667
  CrossrefPubMedGoogle Scholar
• 35 Qiu YG, Chen JZ, Zhu JH et al. Differential effects of morning or evening dosing of amlodipine on circadian blood pressure and heart rate. Cardiovasc Drugs Ther 2003; 17: 335-341
  CrossrefPubMedGoogle Scholar
• 36 Reiter RJ, Tan DX, Korkmaz A. The circadian melatonin rhythm and its modulation: possible impact on hypertension. J Hypertens Suppl 2009; 27: 17-20
  CrossrefPubMedGoogle Scholar
• 37 Rudic RD, McNamara P, Reilly D et al. Bioinformatic analysis of circadian gene oscillation in mouse aorta. Circulation 2005; 112: 2716-2724
  CrossrefPubMedGoogle Scholar
• 38 Schmieder RE, Schrader J, Zidek W et al. Low-grade albuminuria and cardiovascular risk: what is the evidence?. Clin Res Cardiol 2007; 96: 247-257
  CrossrefPubMedGoogle Scholar
• 39 Smolensky MH, Hermida RC, Ayala DE et al. Administration-time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension. Blood Press Monit 2010; 15: 173-180
  CrossrefPubMedGoogle Scholar
• 40 Staessen JA, Thijs L, Fagard R et al. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators. JAMA 1999; 282: 539-546
  CrossrefPubMedGoogle Scholar
• 41 Storch KF, Lipan O, Leykin I et al. Extensive and divergent circadian gene expression in liver and heart. Nature 2002; 417: 78-83
  CrossrefPubMedGoogle Scholar
• 42 Svensson P, de Faire U, Sleight P et al. Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE Substudy. Hypertension 2001; 38: E28-32
  CrossrefPubMedGoogle Scholar
• 43 Takahashi JS, Hong HK, Ko CH et al. The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev Genet 2008; 9: 764-775
  CrossrefPubMedGoogle Scholar
• 44 Tofler GH, Brezinski D, Schafer AI et al. Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death. N Engl J Med 1987; 316: 1514-1518
  CrossrefPubMedGoogle Scholar
• 45 Weinert D, Sitka U, Minors DS et al. The development of circadian rhythmicity in neonates. Early Hum Dev 1994; 36: 117-126
  CrossrefPubMedGoogle Scholar
• 46 Young ME, Razeghi P, Taegtmeyer H. Clock genes in the heart: characterization and attenuation with hypertrophy. Circ Res 2001; 88: 1142-1150
  CrossrefPubMedGoogle Scholar
• 47 Zeng J, Jia M, Ran H et al. Fixed-combination of amlodipine and diuretic chronotherapy in the treatment of essential hypertension: improved blood pressure control with bedtime dosing-a multicenter, open-label randomized study. Hypertens Res 2011; 34: 767-772
  CrossrefPubMedGoogle Scholar